Preparation of dicyanostilbenes



Patented July 11, 1944 UNITED STATES PATENT OFFICE PREPARATION OF DICYANOSTILBENES Harry James Barber, Gidea Park, Romford, England, assignor to May & Baker Limited, Dagenham, Essex, E ngland, a British company No Drawing. Applicati rial No. 410,446. In

The present invention is for improvements in orir'elating to the production of dicyanostilbenes which are of value as starting materials for the preparation of the therapeutically valuable diamidinostilbenesdescribed in'U. S. Patent'No.

The objects of my invention are to provide new on September 11, 1941, Se-

Great Britain September and'advantageousjmethods for the production of dicfyanostilbenes and to provide an improved manufacture of te'trabrornodiphenylethanes which can be employed as starting material in the said methods;

I have found that dicyanostilbenes can be prepared f by "reacting 4,4-{u,fi tetrabromo-diphenylconversion of the fdibromo-stilbeue to the corresponding dicyanocompound.

"When the cuprous salt. employed is cuprous cyanide, the two process steps may, with adv'antag'e, befcombin'ed, i. e., by using the cuprous yama m-an excess over that amount required to produce the dibromo-stilbene such that the two remaining bromine: atoms are converted into organic cy no groupswith the production of the required dicyand-stilbene. "Ihe reaction, which is surprising, proceeds smoothly and gives an almost quantitative yield of the required dicyanostilbene. The exact mechanism of the reaction is unknown to me but the excess cyanide not required for the two organic cyano groups is probably eliminated partly as cyanogen or cyanogen bromide with the copper remaining as cupric bromide or cupric bromocyanide.

In this modification, it may be desirable to employ the cuprous cyanide in an excess over that amount required for the complete conversion of the tetra-bromo-diphenylethane into the dietano-stilbene, i. e., in excess of four molecules per molecule of the tetrabromo compound.

The 4,4'-a,por 2,4-u,p-tetra-bromo-diphenylethane employed as starting material is preferably prepared by the tetra-bromination of afidiphenylethane in acetic acid, the unexpected 8 Claims. (01. 260-465) discovery hai ing been made that, whereas bro-.

mination of ap-diphenylethane in solvents such as' chloroform; carbon disulphide, carbon tetrachloride yields only up-dibromodiphenylethane, bromination in acetic acid gives 4,4 -a,[3-dibromodiphenylethane together with the 2,4-a,p-isomer, which isomers are readily separated.

The following examples illustrate the method of carrying out the process in practice, but it is to be understood that the invention is in no way limited to the details givenin these examples.

Example 1 300 gms. of e-;8=diphenylethane were dissolved in 3300 cc. of glacial acetic acid by warming slightly and then cooling? 160 cc. of water were added followed'by 400 cc. (1200 gins.) of bromine rapidly with shaking; Themixture was then heated to boiling and lition for 2-3 hours. Thetetrabromo compound which'settled as avery heavy crystalline solid was isolated by pouring or siphoning off the hot supernatant liquoriflAfter washing with a little hot acetic acid, it was obtained pure. It was identical with the substance described by Wislicenus,

(Ben 41.4130) from bromine and 4,4-dibromostilbene. On cooling the acetic acid solution 2,4- (1, 8tetrabromo diphenylethane separated. M. Pt. l'-170 C. with decomposition.

. Example 2 gms. of 4,4-a,p tetrabromodiphenylethane prepared as described'in Example 1 were mixed with 63 gms. of cuprous chloride and 250 cc. of pyridine. The masswas mixed thoroughly and boiled for 1-2 hours under reflux. The mass was then poured with stirring into 1000 cc. of hydrochloric acid S."G. 1.16 and the 4,4=-dibromostilbene filtered oft from the hot mixture. It can be purified by crystallisation or it may be used directly for the preparation of dicyanostilbene as described in Example 5. Similarly 231-11-5- tetrabromodiphenylethane gav 2 4 -dibromostilbene. B. Pt. -195 C./2 mm. M. Pt. 84- 85 C.

Example 3 200 gms. of 4,4-a,,B-tetrabromo-diphenylethane, 224 gms. of cuprous cyanide and 225 cc. of pyridine were mixed thoroughly and heated in a metal bath at 2'00-210 C. for 1 /2 hours. Frothing occurs and the temperature of the mixture remained at about C. As frothing diminished the temperature fell slightly. The contents of the flask were cooled slightly and 480 cc. of pyridine were added and the whole boiled for 5 minmaintained in gentle ebul- 'tetrabromo diphenylethane tetrabromodiphenylethane.

Example 4 100 gins. of 4,4'-a- 3-tetrabromodiphenyletharie were mixed thoroughly with 36 gms. of cuprous cyanide and 300 cc. of pyridine andwarmed gra'd- I ually to boiling. A vigorous reaction set in and;

when it had moderated, it was completed by boiling under reflux for 1 /2 hours. mcstilbene can be isolated by any convenient process such as is described in Example 3.

Example 5 4,4'-dibromostilbene; G'O'gms. of cuprous cyanide and 65"gms. of "pyridine wereh'eated to 190- 200 C. for 1 hour. The melt was then stirred into warm hydrochloric acids. G. 1.16 and the crude 4,4'-dicyanostilbene washed with-hydrochloric acid to free from'copper'salts. It can be purified as described in'Example 2.

' In this specification the molecular formula of cuprouscyanide is'understood'to be Cu-CN.

I claim: 1. Process for the production of a member of the group, consisting of 4:4'-dicyano-stilbene and '2,4-dicyano-stilbenecomprising reacting the corresponding member of the group consisting of 4:4"-az,fi-tetrabromo-diphenylethane and 2,4-u,'fltetrabrbmo diph'enylethane with a cuprous salt, whereby the corresponding" dibromo stilbene is formed, reacting the latter with cuprous cyanide, and separating the resulting 'dicyano-stilbene from the reaction product.

2. Process for the production of a member of the group consisting of 4:4'dicyano-stilbene and 2,4 dicyano-stilbene comprising reaoting'the corresponding member of the group consisting of 4 4-afi tetrabromo-diphenylethane and -2,4'-u,fitetrabromo diphenylethane with a cuprous salt selected from the class consisting of cuprous chloride, cuprous bromide" and cuprous cyanide, whereby the corresponding dibromo-stilbene is formed, reacting the latter with cuprous cyanide,

and separating the resulting dicyano-stilbene from'the reaction product. I 3. Process for'th'e' production of a member of the group consisting'ot iA' dicyano-stilbene and 2A -dicyano stilbene'comprising reacting the corresponding member of the group consisting of 4:4'-dgB tetrabromo-diphenylethane and 2,4'-oz,,3 with cuprous cyanide in the proportion of four mols per mol of the said The 4,4'-dibroresponding member of the member, and separating the resulting dicyanostilbene from the reaction product.

4. Process for the production of a member of the group consisting of 4;4-dicyano-stilbene and 2,4'-dicyano-stilbene comprising reacting one mol equivalent of the corresponding member of the group consisting of 4:4-a, 3-tetrabrom0-diphenylethane and 2,4' a,e-tetrabromo-diphenylethane with two mol equivalents of cuprous cyanide, reacting the product with a further two mol equivalents of cuprous cyanide, and separating the resulting dicya'no-stilbene from the reaction product. r a

5.' Process'for+the production of a member of the-groupconsisti-ng of 4:4'-dicyano-stilbene and 2,4.--dicyano-stilbene comprising reacting the corgroup consisting of 4: l-u, 3-tetrabromo-diphenylethane and 2,4'-a,/3- tetrabromo-diphenylethane with cuprous cyanide in excess of four mol equivalents per mol equivalent of the corresponding member, and separating the resulting dicyano-s'tilb'enefrom the reaction product.

6. Process for the production of a member of the group consisting of 4:4'-dicyanostilbne and 2,4-dicyano -stilbene comprising reacting th'ecorresponding member of the group consisting of 4 4-11,,8-tetrabromo diphenylethane and 2;4"-d;fltetrabromo-diphenylethane with a cuprous salt selected from "the class consisting of" cuprous chloride, cuprous bromide and cuprous cyanide, the said cuprous salt being employed as a solution in an organic solvent selectedfrom' the group consisting of pyridine and 'quinoline, whereby the corresponding dibromo-stilbehe is'formed, reactingfthelatter with cuprous cyanide, and separating the resulting dicyano-stilbenefroin the reaction product.

71Process 'for-th'e production of"amember of the group consistingof 4': 4"-'dicyano'-'stilbene and 2,4' dicyano-stilbene'comprising'reactingthecorresponding member oft'he group consisting'bf 4'24-a,p-tetrabromo diphenylethane and 2,4"-",j8- tetrabromo diphenylethane with a cuprous "cyanide in the'proportion' of four' mols'per'm'olof the said member; the cuprous cyanide being employed in the form of asolution in'anprgani'c solventselectedfrom' the-group consistin'g'of py'ri dine and quinoline;-and separatingthemesuitmg 'dicyano-stilbenefromthe reaction product;

' -8; In aprocess forthe' production of 'dicyanostilbenes from tar-member of th'e group consisting of 4,4 lhtetrabromo=diphenylethane"and214"- e,';3-tetrabrom0 diphenylethanejthestepcoinpfising the reductionofthe saidmemberwith atwo -molequivalent" of -a' 'cuprous'salt', whereby t'h'e corresponding dibromo=stilbene is 'formedas'an intermediate: r g r r HARRY JAMES BARBER; 

